Exploring the association between urticaria subtypes, anxiety, and depression and potential role of gut microbiota.

AIMS: In observational studies, the causal relationship between urticaria and the risk of psychiatric disorders (anxiety and depression) remains inconclusive. Furthermore, there is growing evidence that gut microbiota (GM) contributes to the pathogenesis of urticaria. This study aimed to assess the causal relationships between the genetically predicted urticaria subtypes and psychiatric disorders and further examined the role of GM in influencing the risk of these urticaria subtypes.

METHODS

We conducted a meta-analysis of observational studies identified from four databases to evaluate the associations between urticaria, anxiety, and depression over the past decade. In addition, we estimated the genetic correlation and causality between genetically predicted urticaria subtypes and psychiatric disorders using linkage disequilibrium score regression and Mendelian Randomization (MR) analyses. Finally, univariable two-sample MR and multivariable MR analyses were employed to evaluate the combined and independent effects of GM from two datasets on urticaria subtypes associated with psychiatric disorders.

RESULTS

Thirteen observational studies comprising 7321 participants were included in the meta-analysis. There was a positive association between urticaria and anxiety risk (n = 13, OR: 3.96; 95%CI: 2.90-5.41) as well as depression risk (n = 12, OR: 3.03; 95%CI: 2.30-4.01). The MR results indicated that idiopathic urticaria increased the risk of anxiety (OR = 1.14; 95%CI = 1.01-1.28; P = 3.31 × 10-2), while allergic urticaria increased the risk of major depressive disorder (OR = 1.07; 95%CI = 1.02-1.13; P = 6.65 × 10-3). Our analysis identified nineteen gut bacterial taxa that were causally associated with idiopathic and allergic urticaria. Notably, Intestinibacter and Victivallales were strongly associated with an increased risk of allergic urticaria, even after accounting for the effect of smoking or alcohol consumption in the multivariable MR analysis. FamilyXIIIAD3011group and Bacteroides vulgatus were found to exert protective roles in idiopathic urticaria.

CONCLUSIONS

The study provides evidence for the association between urticaria subtypes and psychiatric disorders, complementing existing observational studies. In addition, our study implies the involvement of gut microbiota in idiopathic and allergic urticaria. However, the specific mechanisms of bacterial action remain to be clarified.